Correspondence

Research Letter

Urinary Sediment Findings in Acute Interstitial Nephritis

La nefritis intersticial aguda (NIA) está caracterizada por un infiltrado inflamatorio, edema y tubulitis en el intersticio renal que habitualmente condiciona un deterioro agudo de la función renal. La NIA se refiere a la forma aguda de la enfermedad que presenta un rápido deterioro de la función renal, mientras que las formas crónicas tienen un curso más prolongado, con mayor fibrosis detectada mediante histología. Por lo tanto, el diagnóstico definitivo de ambas patologías es histológico, ya que en la actualidad no se dispone de marcadores no invasivos para su confirmación o exclusión. La incidencia exacta es muy difícil de establecer, pero oscila entre un 5%-27%, con un incremento progresivo de la incidencia principalmente en ancianos, lo que puede reflejar una mayor exposición de los pacientes de edad avanzada a fármacos y otros factores desencadenantes. Actualmente las causas de la NIA han cambiado drásticamente, siendo ahora los agentes farmacológicos la etiología más común (más del 75%).

Acute interstitial nephritis (AIN) is characterised by an inflammatory infiltrate, oedema and tubulitis in the renal interstitial, and it usually leads to acute deterioration of kidney function. AIN refers to the acute form of the disease which causes swift deterioration of kidney function, while the chronic forms have a longer course in which histology detects more fibrosis. The definitive diagnosis of both pathologies is therefore histological, as there are currently no non-invasive markers to confirm or exclude them. Although its exact incidence is very hard to determine, it varies from 5%-27%, progressively increasing in incidence mainly in the elderly, which may be due to their increasing exposure to drugs and other trigger mechanisms. The causes of AIN have undergone a drastic change, as now the most common aetiology consists of pharmacological agents (more than 75%).

Asymmetric bioreductions catalyzed by ketoreductases have shown considerable potential in the synthesis of chiral alcohols. However, the synthesis routes of (1S)-2-chloro-1-(3, 4-difluorophenyl) ethanol ((S)-CFPL), a key chiral intermediate in the synthesis of ticagrelor, still pose significant challenges in term of unsatisfactory substrate loading and production cycle. In this study, a structure-guided rational design was applied to a ketoreductase from Candida glabrata (CgKR1) for the asymmetric reduction of the ketone precursor 2-chloro-1-(3, 4-difluorophenyl) ethanone (CFPO). A number of mutants were obtained with remarkably improved activity and inversed stereoselectivity compared with CgKR1-WT. In particular, F92V/Y208T mutant and F92T/Y208V mutant exhibited strict S-stereoselectivity and extremely high catalytic activity for CFPO. In addition, CFPO with the concentration of 200 g/L can be completely converted into (S)-CFPL on a preparative scale (5.0 g, 92.8% isolated yield) in 4 h through optimizing some parameters in the reduction process, delivering a high space-time yield (STY) of 1200 g L⁻¹ day⁻¹. This study not only provides insight into the relationship between the structure and function of CgKR1, but also establishes an efficient enzymatic process for the biocatalytic synthesis of crucial chiral intermediate (S)-CFPL of ticagrelor.

The examination of the urinary sediment of a 64-year-old woman showed the presence of three different types of crystals, all with unusual morphology, which could not be identified with bright field microscopy, polarized light, and the knowledge of urine pH (7.5). The use of microscopic infrared spectroscopy, Raman spectroscopy and energy dispersive X-ray spectroscopy led to the identification of the three types of crystals as calcite, vaterite and aragonite, which are all variants of calcium carbonate crystals. This paper confirms the complex morphology and nature that urinary crystals may at times have and the utility of advanced infrared spectroscopy techniques for their identification.